Among the ion channels, potassium channels are the largest and most diverse, being found in a variety of animal cells such as nervous, muscular, glandular, immune, reproductive, and epithelial tissue. These channels allow the flow of potassium in and/or out of the cell under certain conditions. These channels are regulated, e.g., by calcium sensitivity, voltage-gating, second messengers, extracellular ligands, and ATP-sensitivity.
Dysfunction of potassium channels, as well as other ion channels, generates loss of cellular control and results in altered physiological functioning and disease conditions. Because of their ability to modulate ion channel function and/or regain ion channel activity in acquired or inherited channelopathies, potassium channel modulators are being used in the pharmacological treatment of a wide range of pathological diseases and have the potential to address an even wider variety of therapeutic indications.
The small conductance calcium-activated potassium channels (SK channel) are a subfamily of Ca2+-activated K+ channels and the SK channel family contains 4 members—SK1, SK2, SK3, and SK4 (often referred to as intermediate conductance). The physiological roles of the SK channels have been especially studied in the nervous system, where for example they are key regulators of neuronal excitability and of neurotransmitter release, and in smooth muscle, where they are crucial in modulating the tone of vascular, broncho-tracheal, urethral, uterine or gastro-intestinal musculature.
Given these implications, small molecule modulators of potassium ion channels could have potentially powerful influence in the modulation and control of numerous consequences of a variety of conditions.